Persistence of smoking induced non-small cell lung carcinogenesis by decreasing ERBB pathway-related microRNA expression

Thorac Cancer. 2019 Apr;10(4):890-897. doi: 10.1111/1759-7714.13020. Epub 2019 Mar 13.

Abstract

Background: Tobacco use is responsible for approximately 80-90% of non-small cell lung cancer cases. A large evidence base has shown that the ERBB pathway is associated with the occurrence of lung cancer. However, the mechanisms of how smoking activates the ERBB pathway have yet to be explained. We hypothesized that microRNAs may induce ERBB pathway activity during the process of lung cancer carcinogenesis.

Methods: We analyzed microRNA array data from the Gene Expression Omnibus and the Kyoto Encyclopedia of Genes and Genomes to determine any associations between genes and smoking in three groups of patients with NSCLC: smokers, former smokers, and non-smokers.

Results: The interaction network among miRNAs, including hsa-mir-185-3p, hsa-mir-4295, hsa-mir-4288, and hsa-mir-613, promotes lung cancer development by affecting the ERBB pathway.

Conclusion: Our findings provide evidence to explain the mechanism of lung cancer development in smokers.

Keywords: EGFR; lung cancer; microRNA; smoking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / mortality
  • ErbB Receptors / metabolism
  • Female
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / mortality
  • Male
  • MicroRNAs / genetics*
  • Signal Transduction*
  • Smoking / adverse effects*
  • Smoking / genetics
  • Smoking / metabolism
  • Smoking / mortality
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • MIRN185 microRNA, human
  • MIRN4288 microRNA, human
  • MIRN4295 microRNA, human
  • MIRN613 microRNA, human
  • MicroRNAs
  • ErbB Receptors